Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
Breast Cancer, Neoplasm, Breast, Breast Diseases
About this trial
This is an interventional prevention trial for Breast Cancer focused on measuring LCZ696, Sacubitril/Valsartan, Magnetic Resonance Imaging, Echocardiography, Cardio-oncology, Breast Cancer, Cardiotoxicity, Anthracyclines, Trastuzumab, Heart failure, Cardioprotection
Eligibility Criteria
Inclusion Criteria:
- Written informed consent
- Female gender, aged 18 years and over
- Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (ER, PR, HER2, Ki67)
- Ability to take oral medication and willingness to adhere to the planned regimen
- Tumor grade IA-IIIC or oligometastatic grade IV
- Radical treatment plan including surgery
- Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and/or anti-HER2 drugs
- ECOG 0-2 general status
- LVEF ≥ 50% as assessed by echocardiography
- Sinus rhythm
Exclusion Criteria:
- Prior anthracycline-based chemotherapy and/or left-sided radiotherapy (prior to diagnosis of the cancer being the present cause of therapy)
- Clinically relevant HF (NYHA II-IV)
- MI within the last < 3 months
- Symptomatic hypotension or SBP < 90 mmHg
- Significant valvular disease, symptomatic coronary artery disease (CCS>2), significant AV block, symptomatic sinus node dysfunction
- Expected survival <12 months
- GFR<30 ml/min/1.73 m2 (screening visit)
- K+>5.5mmol/L (screening visit)
- Contraindications to ACE-I/ARB or LCZ696 if not listed among criteria
- Active untreated liver disease
- Pregnancy
- Contraindications to cardiac MRI, including allergy to gadolinium-containing contrast agent or presence of implanted materials or devices prohibited for MRI
- Conditions/circumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug/alcohol dependence, poorly controlled mental illness)
Sites / Locations
- Regional Cancer Centre in Opole
- Maria Sklodowska-Curie Institute - Oncology Centre (MSCI), Gliwice Branch
- Silesian Center for Heart Diseases
- Holy Cross Cancer Centre, Cardio-Oncology Division
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Experimental: Sacubitril/Valsartan
Placebo
After assessment of the tolerance of the drug during the single-blind period, during the which the starting dose of the drug of 100 mg b.i.d. should be increased after two weeks to the target dose 200 mg b.i.d, the patients will be randomized in 1:1 ratio to either intervention or placebo group. In the experimental arm, the patients after randomization will receive the dose 200 mg b.i.d of sacubitril/valsartan for the course of the study. If the patients does not tolerate the target dose of 200 mg b.i.d., the reduction of the drug dose to 100 mg b.i.d. will be possible at the discretion of the physician-in-charge.
After assessment of the tolerance of the drug during the single-blind period, during the which the starting dose of the drug of 100 mg b.i.d. should be increased after two weeks to the target dose 200 mg b.i.d, the patients will be randomized in 1:1 ratio to either intervention or placebo group. In the placebo arm, the paitents will receive the matching placebo with an identical strategy of dose reduction as in the intervention group, at the discretion of the physician-in-charge.